US2007202097A1PendingUtilityA1

Monoclonal Antibodies That Recognise Mucosal Addressin Cell Adhesion Molecule-1 (Madcam-1), Soluble Madcam-1 And Uses Thereof

49
Individually held — no corporate assignee on recordPriority: Mar 10, 2003Filed: Mar 10, 2004Published: Aug 30, 2007
Est. expiryMar 10, 2023(expired)· nominal 20-yr term from priority
Inventors:Geoffrey Wayne KrissansenEuphemia LeungKlaus Lehnert
C07K 16/2803
49
PatentIndex Score
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Cited by
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Claims

Abstract

The present application describes novel monoclonal antibodies, fragments and derivatives thereof which recognise mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Also described are methods which utilise the monoclonal antibodies. Further, a soluble form of MAdCAM-1 is described as well as methods which utilise its presence in a subject.

Claims

exact text as granted — not AI-modified
1 - 31 . (canceled)  
   
   
       32 . A monoclonal antibody having substantially the binding characteristics of an antibody designated 17F5 produced by hybridoma ATCC PTA-5010, or a fragment or derivative of said monoclonal antibody.  
   
   
       33 . A monoclonal antibody having substantially the binding characteristics of an antibody designated 377D10 produced by hybridoma ATCC PTA-5007, or a fragment or derivative of said monoclonal antibody.  
   
   
       34 . A monoclonal antibody having substantially the binding characteristics of an antibody designated 314G8 produced by hybridoma ATCC PTA-5008, or a fragment or derivative of said monoclonal antibody.  
   
   
       35 . A monoclonal antibody having substantially the binding characteristics of an antibody designated 201F7 produced by hybridoma ATCC PTA-5009, or a fragment or derivative or said monoclonal antibody.  
   
   
       36 . A monoclonal antibody having substantially the binding characteristics of an antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or a fragment or derivative of said monoclonal antibody.  
   
   
       37 . A monoclonal antibody, fragment or derivative thereof having substantially the binding characteristics of an antibody designated, 
 17F5 produced by hybridoma ATCC PTA-5010;    377D10 produced by hybridoma ATCC PTA-5007;    314G8 produced by hybridoma ATCC PTA-5008;    201F7 produced by hybridoma ATCC PTA-5009; or    355G8 produced by hybridoma ATCC PTA-5011; and wherein the antibody, fragment or derivative thereof binds to soluble native human MAdCAM-1.    
   
   
       38 . The monoclonal antibody, fragment or derivative of  claim 37 , wherein the antibody, fragment or derivative thereof is capable of detecting MAdCAM-1 present in osteoarthritic synovium.  
   
   
       39 . The monoclonal antibody, fragment or derivative of  claim 37 , wherein the antibody, fragment or derivative thereof has the isotype 1gG1 (kappa).  
   
   
       40 . An antibody, fragment or derivative thereof, wherein the antibody, fragment or derivative thereof recognises the first 1g domain of MAdCAM-1, and has substantially the binding characteristics of an antibody designated 
 377D10 produced by hybridoma ATCC PTA-5007;    314G8 produced by hybridoma ATCC PTA-5008;    20G17 produced by hybridoma ATCC PTA-5009; or    355G8 produced by hybridoma ATCC PTA-5011.    
   
   
       41 . An antibody, fragment or derivative thereof as claimed in  claim 40 , wherein the antibody, fragment or derivative thereof blocks the interaction of MAdCAM with the integrin α4β7.  
   
   
       42 . An antibody, fragment or derivative thereof as claimed in  claim 41 , wherein the antibody, fragment or derivative blocks the interaction of MAdCAM with an α4 integrin.  
   
   
       43 . An antibody, fragment or derivative thereof as claimed in  claim 32 , wherein the antibody, fragment or derivative thereof recognises the mucin domain of MAdCAM-1.  
   
   
       44 . A monoclonal antibody selected from the group consisting of an antibody designated 17F5 produced by hybridoma ATCC PTA-5010, 
 an antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    an antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    an antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    an antibody designated 355G8 produced by hybridoma ATCC PTA-5011,    or a fragment or derivative of said antibody.    
   
   
       45 - 48 . (canceled)  
   
   
       49 . A hybridoma cell line characterised by a deposit selected from the group consisting of ATCC PTA-5010, ATCC PTA-5007, ATCC PTA-5008, ATCC PTA-509, ATCC PTA-5011.  
   
   
       50 - 53 . (canceled)  
   
   
       54 . A method of blocking the interaction of MAdCAM-1 with the integrin α4β7 the method comprising at least the step of bringing said MAdCAM-1 into contact with one or more monoclonal antibody chosen from 
 a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011,    or an antibody having substantially the binding characteristics of one of said antibodies,    or a fragment or derivative thereof or a fragment or derivative thereof.    
   
   
       55 . The method of  claim 54  wherein the method is for blocking leukocyte adhesion to MAdCAM-1.  
   
   
       56 . A method of detecting the presence of MAdCAM-1 in a sample, the method comprising at least the steps of: 
 a. placing the sample in contact with one or more of the monoclonal antibodies chosen from    a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010,    a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or    an antibody having substantially the binding characteristics of one of said antibodies or a fragment or derivative thereof    for sufficient time to allow binding between the one or more antibodies or fragments or derivatives thereof and MAdCAM-1 if present in the sample; and,    b. detecting whether or not binding has occurred;    wherein binding is indicative of the presence of MAdCAM-1.    
   
   
       57 . A method of diagnosing or monitoring inflammation in a subject, the method comprising at least the steps of: 
 a. placing the sample in contact with one or more of the monoclonal antibodies chosen from    a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010    a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or    an antibody having substantially the binding characteristics of one of said antibodies, or a fragment or derivative thereof    for sufficient time to allow binding between the one or more antibodies or fragments or derivatives thereof with MAdCAM-1 if present in the sample;    b. detecting the level of binding, wherein the level of binding is indicative of the level of MAdCAM-1 present in the sample;    c. comparing the level of MAdCAM-1 present in the sample to a base level or standard.    
   
   
       58 . The method of  claim 57  wherein a statistically significant increase in the level of MAdCAM-1 above the base level or standard is diagnostic of inflammation.  
   
   
       59 . The method of in  claim 56  or  57  wherein the sample is a tissue or fluid sample.  
   
   
       60 . The method of  claim 59  wherein the fluid sample is serum, plasma or urine.  
   
   
       61 . The method of  claim 56  or  57  wherein the method involves one or more of: 
 ELISA;    RIA;    Immunoprecipitation;    Western blotting;    Immunohistochemical staining;    Affinity Chromatography;    Competitive binding assays; and    Agglutination assays.    
   
   
       62 . The method of  claim 61  wherein the method involves ELISA and the ELISA is a sandwich ELISA utilising a capture antibody and a detection antibody, wherein: 
 a) the capture antibody is chosen from a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010, a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or an antibody having substantially the binding characteristics of one of said antibodies, or fragments or derivatives thereof; and,    b) the detection antibody is chosen from    a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    or an antibody having substantially the binding characteristics of one of said antibodies,    or a fragment or derivative thereof.    
   
   
       63 . The method as claimed in  claim 61  wherein the method involves ELISA and the ELISA is a sandwich ELISA utilising a capture antibody and a detection antibody, wherein: a) the capture antibody is chosen from 
 a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    or an antibody having substantially the binding characteristics of one of said antibodies    or fragment or derivative thereof; and,    b) the detection antibody is chosen from    a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010, an antibody a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or an antibody having substantially the binding characteristics of one of said antibodies, or fragments or derivatives thereof.    
   
   
       64 . A method as claimed in any one of claims  54 ,  56  or  57  wherein the MAdCAM-1 is soluble MAdCAM-1.  
   
   
       65 . A method as claimed in any one of claims  54 ,  56  or  57  wherein the MAdCAM-1 is membrane-bound MAdCAM-1.  
   
   
       66 . A method as claimed in  claim 56  or  57  wherein the method is for diagnosing or monitoring one or more of the following inflammatory disorders: appendicitis, pancreatitis, inflammatory bowel disease including Crohn's disease and ulcerative colitis, inflammatory liver disease, diabetes, multiple sclerosis and other demyelinating diseases, duodenal ulcers, arthritis, asthma and other allergic inflammatory diseases, atherosclerosis, and inflammation associated with transplantation and chronic infection.  
   
   
       67 . A method as claimed in  claim 66  wherein the method is for diagnosing or monitoring Crohn's disease.  
   
   
       68 . A method as claimed in  claim 66  wherein the method is for diagnosing or monitoring osteoarthritis.  
   
   
       69 . A pharmaceutical composition comprising at least one or more of the a monoclonal antibody selected from the group consisting of 
 a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007;    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008;    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009; and    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011; or    an antibody having substantially the binding characteristics of one or said antibodies,    or a fragment or derivative thereof in combination with one or more pharmaceutically acceptable diluents, carriers and/or excipients.    
   
   
       70 . A method for the treatment of inflammation in a subject the method comprising at least the step of administering to said subject the pharmaceutical composition of  claim 69 .  
   
   
       71 . A method as claimed in  claim 70 , wherein the pharmaceutical composition is for the treatment of one or more of the following inflammatory disorders: appendicitis, pancreatitis, inflammatory bowel disease including Crohn's disease and ulcerative colitis, inflammatory liver disease, diabetes, multiple sclerosis and other demyclinating diseases, duodenal ulcers, arthritis, asthma and other allergic inflammatory diseases, atherosclerosis, and inflammation associated with transplantation and chronic infection.  
   
   
       72 . A method as claimed in  claim 71 , wherein the pharmaceutical composition is for the treatment of Crohn's disease.  
   
   
       73 . A method as claimed in  claim 71 , wherein the pharmaceutical composition is for the treatment of osteoarthritis.  
   
   
       74 . A kit for detecting MAdCAM-1 in a sample or diagnosing or monitoring inflammation in a subject, the kit comprising at least one or more of the monoclonal antibodies or 
 a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010,    a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007,    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008,    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011, or    an antibody having substantially the binding characteristics of one of said antibodies or a fragment or derivative thereof.    
   
   
       75 . A kit as claimed in  claim 74 , wherein it includes a capture antibody and a detection antibody, wherein: 
 a) the capture antibody is chosen from a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011,    or an antibody having substantially the binding characteristics of one of said antibodies; and,    b) the detection antibody is chosen from    a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007;    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008;    monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009; and    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011;    or an antibody having substantially the binding characteristics of one or more of said antibodies,    a fragment or derivative thereof.    
   
   
       76 . A kit as claimed in  claim 74  wherein it includes a capture antibody and a detection antibody, wherein: a) the capture antibody is chosen from 
 a monoclonal antibody designated 377D10 produced by hybridoma ATCC PTA-5007;    a monoclonal antibody designated 314G8 produced by hybridoma ATCC PTA-5008;    a monoclonal antibody designated 201F7 produced by hybridoma ATCC PTA-5009; and    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011;    or an antibody having substantially the binding characteristics of one or more of said antibodies; and, b) the detection antibody is chosen from    a monoclonal antibody designated 17F5 produced by hybridoma ATCC PTA-5010,    a monoclonal antibody designated 355G8 produced by hybridoma ATCC PTA-5011;    or an antibody having substantially the binding characteristics of one or more of said antibodies or fragment or derivative thereof.    
   
   
       77 . A kit as claimed in  claim 74 , wherein the kit further comprises one or more control samples comprising a known level of MAdCAM-1 or a fragment or derivative thereof.

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